Friday, 18 July 2014

The demise of 'Mouse Utopia' reinterpreted as mutation accumulation by Michael A Woodley

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The so-called Mouse Utopia experiment was conducted from 1968 by John B Calhoun

http://en.wikipedia.org/wiki/John_B._Calhoun

The idea was that four breeding pairs of mice were allowed to reproduce freely in a 'utopian' environment with ample food and water; no predators; no disease; comfortable temperature, conditions and space. What happened is described by the author:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1644264/pdf/procrsmed00338-0007.pdf


Phase A - 104 days - establishment of the mice in their new environment, then the first litters were born.

Phase B - up to day 315 - exponential population growth doubling every 55 days.

Phase C - from day 315-560 population growth abruptly slowed to a doubling time of 145 days.

Phase D - days 560-920; population stagnant with births just matching deaths. Emergence of many pathological behaviours.

Terminal Phase - population declining to zero. The last conception was about day 920, after which there were no more births, all females were menopausal, the colony aged and all of them died.

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The Mouse Utopia experiment is usually interpreted in terms of social stresses related to 'over-population' crowding - generating pathological behaviours and a loss of the will to live.

But Michael A Woodley suggests that what might be going on is mutation accumulation, and deleterious genes generating a wide range of maladaptive pathologies, incrementally accumulating with each generation; and rapidly overwhelming and destroying the population before any beneficial mutations could emerge to 'save; the colony from extinction. 

So the bizarre behaviours seen especially in Phase D - such as the male 'beautiful ones' who appeared to be healthy and spent all their time self grooming, but were actually inert, unresponsive, unintelligent, uninterested in reproduction - are not adaptations to crowding, but maladaptive outcomes of a population sinking under the weight of mutations.

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The reason why mouse utopia might produce so rapid and extreme a mutation accumulation is that wild mice naturally suffer very high mortality rates from predation.

Therefore, because wild mice are so short-lived, mice are not 'built to last' and have the reputation of being unusually-prone to produce new deleterious mutations (and are therefore extremely prone to cancer, and susceptible to carcinogens - which is why mice are used to test for carcinogens).

Thus mutation selection balance is in operation among wild mice, with very high mortality rates continually weeding-out the new mutations (especially among males) - with typically only a small and relatively mutation-free proportion of the (large numbers of) offspring surviving to reproduce; and a minority of the most active and healthy (mutation free) males siring the bulk of each generation.

However, in Mouse Utopia, there is no predation and all the other causes of mortality are reduced to a minimum - so the frequent mutations just accumulate, generation upon generation - randomly producing all sorts of pathological (maladaptive) behaviours.

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To test whether mutation accumulation is the real explanation for the demise of Mouse Utopia, the original experiment should be repeated but with genetic controls. Woodley is hoping to do this himself.

Also, a variant experiment could perhaps be conducted, which maintained utopian conditions but without allowing overcrowding (e.g. by continually splitting-up the growing community, and creating more and more small colonies - or (see comment below) by random culling).

In other words, the social conditions of Utopian mice would be held constant, while mortality rates would be kept low for multiple generations. 

My prediction would be that the Mouse Utopians would go through phases A, B, C, D and terminal to become extinct even without increased population density/ overcrowding, and due purely to cumulative genetic damage.

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12 comments:

Mangan said...

What occurred to me was that is that today's lab mice are all in "mouse utopia": no predators and they virtually all make it to adulthood. Yet they reproduce and are normal enough, as far as I know. If the mutation load idea is correct, modern lab mice must have a huge load.

John Goes said...

How exactly could one control the genetics?

Bruce Charlton said...

@Dennis - The critical thing is not so much the utopia but the breeding stock. Lab animals are very selectively bred, as I understand it - this achieves artificially what nature achieves by predation etc.

Bruce Charlton said...

@JG - Well, I am assuming that IF there was evidence of mutation accumulation, THEN the behavioural effects could more confidently attributed to genetic change IF the social aspects were controlled.

As for controlling the genetics - the plan could be to increase the population at the same rate and in the same conditions as the original Mice Utopia, but by infusing selectively bred stock (rather than allowing the mice to interbreed and increase ad lib).

Mangan said...

Bruce: makes sense. Most lab mice will never breed, or if they do, their progeny don't.

pyrrhus said...

Fascinating post, thanks Bruce! Yes, perhaps the mutation load point casts some doubt on experiments using lab mice. In any event, I would like to see Mouse Utopia repeated with wild mice.

pumpkinperson said...

Also, a variant experiment could perhaps be conducted, which maintained utopian conditions but without allowing overcrowding (e.g. by continually splitting-up the growing community, and creating more and more small colonies).

In other words, the social conditions of Utopian mice would be held constant, while mortality rates would be kept low for multiple generations.


This would be a good experiment to do, and what could make it especially interesting would be to intelligence test the mice in the first generation (perhaps by measuring how quickly they got through a maze) and then comparing their performance with mice several generations later, to see if the mutation accumulation lowered their intelligence by anything close to 1 SD. It would be fascinating to see the studies of human intelligence decline experimentally replicated in mice.

One could even weigh the brains of the mice after they died to see if there was a decline in brain weight. The correlation between brain size and intelligence in mice is 0.48, very similar to the 0.4 correlation found in humans.

Bruce Charlton said...

@pp- Good ideas.

In fact Michael is, of course, intending to do exactly this kind of thing - since he is an intelligence researcher and that is the underlying reason for trying to replicate Mouse Utopia.

J said...

I presume that the frequent mutations will not just accumulate, generation upon generation, even in the absense of predators. Spontaneous abortions and genetic infertility will cull out most of the defectives. According to the literature, the mouse becomes aggressive in crowded environments, kill the young, dont mate, fight among themselves. Anyway, it would be interesting to have a rerun of that mythical experiment, I bet it will not be repeated.

Bruce Charlton said...

@J - I believe that the understanding of mutation accumulation comes mainly from rapidly dividing simple organisms like bacteria. While lethal mutations are self-eliminating, sub-lethal mutations accumulate.

In Mouse Utopia Woodley assumes that the damaging mutations overwhelmed the population before any beneficial mutations had arisen which might have enabled survival in the Mouse Utopia environment.

Among rapidly diving and simpler bacteria, apparently, a strange new mutant species (or more than one) may arise before extinction - and the bacteria may continue to survive in the long term. Whether this is likely in larger and more complex organisms mice and humans - I don't know. The environment of the earth is big, complex, varied...

drbillorthosphere said...

Why does the colony need to be split? Just sacrifice X% of the colony each generation. You must be careful to sacrifice them at random, obviously, but that should not be a problem.

Actually, this plan gives you additional opportunities for data collection. Don't sacrifice the extra mice all at the same age each generation. Sacrifice then at random (or, if you prefer preset) ages. This way you can look at autopsy for what the abnormalities are and when they develop. If money is unlimited, you could do things like looking at patterns of gene expression in various tissues over the life-cycle of the mice, and how these change as the colony degrades.

Bruce Charlton said...

@dbo - Yes, that should do it - and a lot more cheaply. I was distracted by wanting to know what happened to the genetics of all the divided colonies.